Outcomes and Molecular Features of Brain Metastasis in Gastroesophageal Adenocarcinoma
Authors: Charlton Tsai, Bastien Nguyen, Anisha Luthra, Joanne F. Chou, Lara Feder, Laura H. Tang, Vivian E. Strong, Daniela Molena, David R. Jones, Daniel G. Coit, David H. Ilson, Geoffrey Y. Ku, Darren Cowzer, John Cadley, Marinela Capanu, Nikolaus Schultz, Kathryn Beal, Nelson S. Moss, Yelena Y. Janjigian, Steven B. Maron
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis. <h3>Objectives</h3> To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival. <h3>Design, Setting, and Participants</h3> In this single-institution retrospective cohort study, 68 patients with BrM from GEA diagnosed between January 1, 2008, and December 31, 2020, were identified via review of billing codes and imaging reports from the electronic medical record with follow-up through November 3, 2021. Genomic data were derived from the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets clinical sequencing platform. <h3>Exposures</h3> Treatment with BrM resection and/or radiotherapy. <h3>Main Outcomes and Measures</h3> Overall survival after BrM diagnosis. <h3>Results</h3> Sixty-eight patients (median age at diagnosis, 57.4 years [IQR, 49.8-66.4 years]; 59 [86.8%] male; 55 [85.9%] White) participated in the study. A total of 57 (83.8%) had primary tumors in the distal esophagus or gastroesophageal junction. Median time from initial diagnosis to BrM diagnosis was 16.9 months (IQR, 8.5-27.7 months). Median survival from BrM diagnosis was 8.7 months (95% CI, 5.5-11.5 months). Overall survival was 35% (95% CI, 25%-48%) at 1 year and 24% (95% CI, 16%-37%) at 2 years. In a multivariable analysis, an Eastern Cooperative Oncology Group performance status of 2 or greater (hazard ratio [HR], 4.66; 95% CI, 1.47-14.70;<i>P</i> = .009) and lack of surgical or radiotherapeutic intervention (HR, 7.71; 95% CI, 2.01-29.60;<i>P</i> = .003) were associated with increased risk of all-cause mortality, whereas 3 or more extracranial sites of disease (HR, 1.85; 95% CI, 0.64-5.29;<i>P</i> = .25) and 4 or more BrMs (HR, 2.15; 95% CI, 0.93-4.98;<i>P</i> = .07) were not statistically significant. A total of 31 patients (45.6%) had<i>ERBB2</i>(formerly<i>HER2</i>or<i>HER2/neu</i>)–positive tumors, and alterations in<i>ERBB2</i>were enriched in BrM relative to primary tumors (8 [47.1%] vs 7 [20.6%],<i>P</i> = .05), as were alterations in<i>PTPRT</i>(7 [41.2%] vs 4 [11.8%],<i>P</i> = .03). <h3>Conclusions and Relevance</h3> This study suggests that that a notable proportion of patients with BrM from GEA achieve survival exceeding 1 and 2 years from BrM diagnosis, a more favorable prognosis than previously reported. Good performance status and treatment with combination surgery and radiotherapy were associated with the best outcomes.<i>ERBB2</i>positivity and amplification as well as<i>PTPRT</i>alterations were enriched in BrM tissue compared with primary tumors; therefore, further study should be pursued to identify whether these variables represent genomic risk factors for BrM development.